The floor plate is sufficient for development of the sclerotome and spine without the notochord

Abstract

Danforth'sshort-tail (Sd) mouse is a semi-dominant mutation affecting the development of the vertebral column. Although the notochord degenerates completely by embryonic day 9.5, the vertebral column exists up to the lumber region, suggesting that the floor plate can substitute for notochord function. We previously established the mutant mouse line, Skt(Gt), through gene trap mutagenesis and identified the novel gene, Skt, which was mapped 0.95cM distal to the Sd locus. Taking advantage of the fact that monitoring notochordal development and genotyping of the Sd locus can be performed using the Skt(Gt) allele, we assessed the development of the vertebra, notochord, somite, floor plate and sclerotome in +-+/+-Skt(Gt), Sd-+/+-+, Sd-Skt(Gt)/+-+, Sd-Skt(Gt)/+-Skt(Gt), Sd-+/Sd-+ and Sd-Skt(Gt)/Sd-Skt(Gt) embryos. In Sd homozygous mutants with a C57BL/6 genetic background, the vertebral column was truncated in the 6th thoracic vertebra, which was more severe than previously reported. The floor plate and sclerotome developed to the level of somite before notochord degeneration and the number of remaining vertebrae corresponded well with the level of development of the floor plate and sclerotome. Defects to the sclerotome and subsequent vertebral development were not due to failure of somitogenesis. Taken together, these results suggest that the notochord induced floor plate development before degeneration, and that the remaining floor plate is sufficient for maintenance of differentiation of the somite into the sclerotome and vertebra in the absence of the notochord.

Sonic hedgehog in the notochord is sufficient for patterning of the intervertebral discs

“…A recent report suggested that the floor plate compensates for notochord function beginning at E10.5(Ando et al, 2011). In these experiments, loss of the notochord at E10.5 did not affect vertebral patterning or Pax1 expression in the sclerotome.…”

“…In these experiments, loss of the notochord at E10.5 did not affect vertebral patterning or Pax1 expression in the sclerotome. Lack of a notochord at E10.5 should result in the absence of nuclei pulposi, however, the intervertebral discs were not analyzed in mice that lacked a visible notochord(Ando et al, 2011). …”

Ectopic Expression of Ptf1a Induces Spinal Defects, Urogenital Defects, and Anorectal Malformations in Danforth's Short Tail Mice

“…Heterozygous and homozygous Sd animals display a broad range of abnormalities in the vertebral column, including reduction or absence of the dens axis, reduction of all vertebral bodies in the dorsoventral axis, split vertebrae, and truncation of the caudal vertebral column [4], [5], [6]. The vertebral columns of Sd/Sd and Sd/+ mice are usually truncated at the seventh thoracic and the sixth caudal vertebral body, respectively [7]. The urogenital system in Sd heterozygotes may display malformations ranging from displaced to missing kidneys.…”

In vivo knockdown of Brachyury results in skeletal defects and urorectal malformations resembling caudal regression syndrome

“…Mechanical and genetic manipulations have shown that regional specification of somites depends on secreted factors from the notochord and neural tube (Chiang et al, 1996;Dietrich et al, 1997;Pourquie et al, 1993;Teillet et al, 1998;Teillet and Le Douarin, 1983). Both the notochord and the floor plate produce the morphogen Shh, and its expression in the notochord is essential for induction of the floor plate (Roelink et al, 1994), however, once the floor plate of the neural tube has been established, the notochord is no longer required for vertebral development (Ando et al, 2011). It has recently been shown that Shh is dispensable for vertebral formation after the notochord sheath appears (at approximately E10.0), which is a structure that surrounds the notochord cells, acting as a ''wrapper'' (Choi and Harfe, 2011).…”